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Nearly all men with metastatic hormone-sensitive prostate cancer treated with intermittent androgen deprivation therapy (ADT) experience recurrence within 6 mo of testosterone recovery. We conducted a single-arm phase 2 trial to evaluate whether addition of dual androgen receptor pathway inhibitors (ARPIs) and metastasis-directed stereotactic body radiotherapy (SBRT) to intermittent ADT improves recurrence rates for men with between one and five nonvisceral, extrapelvic metastases on prostate-specific membrane antigen positron emission tomography/computed tomography after prior radical prostatectomy. Patients received 6 mo of androgen annihilation therapy (AAT; leuprolide, abiraterone acetate plus prednisone, and apalutamide) and metastasis-directed SBRT. The primary endpoint was the percentage of patients with prostate-specific antigen (PSA)

Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumors anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges.

Stereotactic body radiotherapy (SBRT) without androgen deprivation therapy (ADT) has lower rates of incontinence and sexual dysfunction, with a small trade-off in bowel bother, compared with prostatectomy. At 2 yr, 50% of men who underwent prostatectomy reported using urinary pads, compared with 6.5% who underwent SBRT, whilst only a modest reduction in the Expanded Prostate Index Composite (EPIC) bowel domain score was seen for SBRT compared with that for prostatectomy. Prostatectomy participants reported worse sexual function at 2 yr. Randomised data on patient-reported outcomes (PROs) for stereotactic body radiotherapy (SBRT) and prostatectomy in localised prostate cancer are lacking. PACE-A compared patient-reported health-related quality of life after SBRT with that after prostatectomy. PACE is a phase 3 open-label, randomised controlled trial. PACE-A randomised men with low- to intermediate-risk localised prostate cancer to SBRT or prostatectomy (1:1). Androgen deprivation therapy (ADT) was not permitted. The coprimary outcomes were the Expanded Prostate Index Composite (EPIC-26) number of absorbent urinary pads required daily and bowel domain score at 2 yr. The secondary endpoints were clinician-reported toxicity, sexual functioning, and other PROs. In total, 123 men were randomised (60 undergoing prostatectomy and 63 SBRT) from August 2012 to February 2022. The median follow-up time was 60.7 mo. The median age was 65.5 yr and the median prostate-specific antigen (PSA) value 7.9 ng/ml; 92% had National Comprehensive Cancer Network (NCCN) intermediate-risk disease. Fifty participants received prostatectomy and 60 received SBRT. At 2 yr, 16/32 (50%) prostatectomy and three of 46 (6.5%) SBRT participants used one or more urinary pads daily (p < 0.001; 15 and two, respectively, used one pad daily); the estimated difference was 43% (95% confidence interval [CI]: 25%, 62%). At 2 yr, bowel scores were better for prostatectomy (median [interquartile range] 100 [100–100]) than for SBRT (87.5 [79.2–100]; p < 0.001), with an estimated mean difference of 8.9 between these (95% CI: 4.2, 13.7); sexual scores were worse for prostatectomy (18 [13.8–40.3]) than for SBRT (62.5 [32.0–87.5]). The limitations were slow recruitment and incomplete 2-yr PRO response rates. SBRT was associated with less patient-reported urinary incontinence and sexual dysfunction, and slightly more bowel bother than prostatectomy. These randomised data should inform treatment decision-making for patients with localised, intermediate-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: The role of local ablative radiotherapy (stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS)) in the management of metastatic breast cancer (mBC) patients remains unclear. This study aimed to assess the efficacy of SBRT/SRS in oligometastatic and oligoprogressive breast cancer patients. Methods: Totally 80 mBC patients with oligometastatic disease (OMD) and 80 with oligoprogressive disease (OPD) to ≤5 metastatic lesions were retrospectively analyzed. The endpoint was overall survival and progression-free survival, and univariate and multivariate analyses were performed for survival analysis. Results: Totally 160 mBC cases (80 OMD and 80 OPD cases) were analyzed, with a total of 291 treated metastases. In the study of OMD, we analyzed 30 cases with oligo-recurrence and 50 cases with sync-oligometastases. The median follow-up time was 46 months, and 1-, 2-, and 3-year OS rates for all patients were 89.8%, 77.6%, and 67.3%, respectively, and the 1-, 2-, and 3-year PFS rates were 71.4%, 44.9%, and 34.7% respectively. In multivariate analysis (MVA), treatment for oligometastases and non-triple-negative status predicted favorable OS. In patients with oligometastases, median OS was 58 months, and 1-, 2-, and 3-year OS rates were 100%, 91.7%, and 83.3%, respectively; median OS in patients with oligoprogression was 35 months, and 1-, 2-, and 3-year OS rates were 80%, 64%, and 52%, respectively. In mBC cases with limited brain metastases administered SRS, poor OS was detected in patient age under 45 years (P = 0.041), triple-negative cases (P = 0.025), and those with OPD (P = 0.022). In OMD, a significant improvement in PFS was observed in the oligo-recurrence group compared to the sync-oligometastases group (P = 0.013). Conclusion: Patients administered local ablative radiotherapy (SBRT/SRS) for oligometastases have better overall survival than those treated for oligoprogression. SBRT/SRS may be beneficial for young and non-triple-negative mBC cases. The presence of oligo-recurrence can predict a favorable prognosis of oligometastases in patients with mBC treated with SBRT/SRS. [ABSTRACT FROM AUTHOR]

In the treatment of primary liver cancer and metastatic liver cancer, stereotactic body radiotherapy (SBRT) can be utilized to administer high doses of radiation for achieving ablative therapeutic effects. Given the singular nature of delivering high-dose radiation through SBRT, a higher level of precision is required in radiation therapy. Particularly, liver cancer is susceptible to positioning errors and respiratory motion, necessitating the implementation of respiratory motion management and image guidance techniques. However, existing accuracy verification methods for radiation therapy primarily rely on phantom studies, making it challenging to conduct in⁃vivo verification during treatment execution. Research has indicated that the liver exhibits corresponding morphological changes in magnetic resonance imaging following exposure to specific doses of radiation therapy, thereby serving as an indicator for assessing treatment accuracy. This article aims to discuss and analyze the principles underlying magnetic resonance imaging alterations after stereotactic body radiotherapy for liver cancer, including their manifestations, timing of appearance, evaluation methodologies for accuracy assessment, clinical challenges encountered during implementation, as well as future directions for development. [ABSTRACT FROM AUTHOR]

Background: The SMILE study addresses a significant need in palliative oncology by evaluating the non-inferiority of a shortened, 3-fraction stereotactic body radiotherapy (SBRT) schedule against the traditional 5-fraction approach for non-spine bone metastases in terms of pain control. Optimizing SBRT could significantly enhance the quality of life for patients by providing effective pain relief while minimizing treatment sessions. Methods: This international, multicenter phase III trial will randomize 162 patients to receive either a 3-fraction regimen (9 Gy per fraction) or a standard 5-fraction regimen (7 Gy per fraction). Outcomes, assessed at 3 months post-treatment, will focus on pain response, quality of life, and control of metastasis. With a hypothesis-driven design, the study will incorporate intent-to-treat and per-protocol analyses, incorporating appropriate measures for data integrity and handling of missing information. Discussion: If the 3-fraction SBRT regimen demonstrates non-inferiority, it could streamline palliative care protocols, reduce patient burden, and set a new standard for treatment, reflecting a patient-centered approach in palliative radiation oncology. Trial registration: The trial has been registered prospectively on ClinicalTrials.gov under the identifier NCT05406063, as of May 3, 2022. [ABSTRACT FROM AUTHOR]

Introduction: Penile metastases (PMs) are a rare clinical presentation mainly related to advanced stages of disease. Considering the low incidence, an optimal treatment approach has not yet been defined; surgery, chemotherapy, and radiotherapy (RT) are different options used in the vast majority with palliative intent. The advances in modern RT can represent an innovative tool in PM management and a curative option. This paper aimed to report the case of a PM patient treated with stereotactic body radiotherapy (SBRT) and perform a systematic literature review of current evidence on the RT approach to PM. Case Presentation: We reported the case of an 80-year-old patient with PM from primary bladder cancer. Following the surgical approach for the primary tumor, evidence of PM was shown, and the patient was admitted to SBRT treatment on PM after an adjuvant RT course on the pelvis. A 25 Gy in 5-fraction SBRT treatment was performed, and a complete clinical response was shown at the first follow-up. A PubMed/MEDLINE and Embase systematic review was carried out. The search strategy terms were [("penile metastasis"/exp OR "penile metastasis" OR (penile AND ("metastasis"/exp OR metastasis))) AND ("radiotherapy"/exp OR radiotherapy)] and only original articles up to October 24, 2023 were considered. Conclusion: A total of 174 studies were obtained using the previously mentioned search strategy, and the analysis was performed on 15 papers obtained following the complete selection process. All reported evidence was focused on the palliative approach of PM, showing good results in terms of symptom control. The potential role of modern RT in the management of PM has yet to be defined. The reported case showed the feasibility and the clinical impact of SBRT in PM treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The spine is the most common site of osseous metastatic involvement. Advances in diagnosing and treating spinal metastasis have improved patient survival and quality of life. There is now a strong focus on customized imaging to enhance treatment planning for tumor ablation and reduce treatment-related complications. This review discusses imaging protocols and findings in the pre- and post-SBRT setting and the imaging features differentiating expected post-SBRT treatment changes from LF. Spine metastases (SMs) are common, arising in 70% of the cases of the most prevalent malignancies in males (prostate cancer) and females (breast cancer). Stereotactic body radiotherapy, or SBRT, has been incorporated into clinical treatment algorithms over the past decade. SBRT has shown promising rates of local control for oligometastatic spinal lesions with low radiation dose to adjacent critical tissues, particularly the spinal cord. Imaging is critically important in SBRT planning, guidance, and response monitoring. This paper reviews the roles of imaging in spine SBRT, including conventional and advanced imaging approaches for SM detection, treatment planning, and post-SBRT follow-up. [ABSTRACT FROM AUTHOR]

Background: Cardiac stereotactic body radiotherapy (CSBRT) is an emerging and promising noninvasive technique for treating refractory arrhythmias utilizing highly precise, single or limited‐fraction high‐dose irradiations. This method promises to revolutionize the treatment of cardiac conditions by delivering targeted therapy with minimal exposure to surrounding healthy tissues. However, the dynamic nature of cardiorespiratory motion poses significant challenges to the precise delivery of dose in CSBRT, introducing potential variabilities that can impact treatment efficacy. The complexities of the influence of cardiorespiratory motion on dose distribution are compounded by interplay and blurring effects, introducing additional layers of dose uncertainty. These effects, critical to the understanding and improvement of the accuracy of CSBRT, remain unexplored, presenting a gap in current clinical literature. Purpose: To investigate the cardiorespiratory motion characteristics in arrhythmia patients and the dosimetric impact of interplay and blurring effects induced by cardiorespiratory motion on CSBRT plan quality. Methods: The position and volume variations in the substrate target and cardiac substructures were evaluated in 12 arrhythmia patients using displacement maximum (DMX) and volume metrics. Moreover, a four‐dimensional (4D) dose reconstruction approach was employed to examine the dose uncertainty of the cardiorespiratory motion. Results: Cardiac pulsation induced lower DMX than respiratory motion but increased the coefficient of variation and relative range in cardiac substructure volumes. The mean DMX of the substrate target was 0.52 cm (range: 0.26–0.80 cm) for cardiac pulsation and 0.82 cm (range: 0.32–2.05 cm) for respiratory motion. The mean DMX of the cardiac structure ranged from 0.15 to 1.56 cm during cardiac pulsation and from 0.35 to 1.89 cm during respiratory motion. Cardiac pulsation resulted in an average deviation of –0.73% (range: –4.01%–4.47%) in V25 between the 3D and 4D doses. The mean deviations in the homogeneity index (HI) and gradient index (GI) were 1.70% (range: –3.10%–4.36%) and 0.03 (range: –0.14–0.11), respectively. For cardiac substructures, the deviations in D50 due to cardiac pulsation ranged from –1.88% to 1.44%, whereas the deviations in Dmax ranged from –2.96% to 0.88% of the prescription dose. By contrast, the respiratory motion led to a mean deviation of –1.50% (range: –10.73%–4.23%) in V25. The mean deviations in HI and GI due to respiratory motion were 4.43% (range: –3.89%–13.98%) and 0.18 (range: –0.01–0.47) (p < 0.05), respectively. Furthermore, the deviations in D50 and Dmax in cardiac substructures for the respiratory motion ranged from –0.28% to 4.24% and –4.12% to 1.16%, respectively. Conclusions: Cardiorespiratory motion characteristics vary among patients, with the respiratory motion being more significant. The intricate cardiorespiratory motion characteristics and CSBRT plan complexity can induce substantial dose uncertainty. Therefore, assessing individual motion characteristics and 4D dose reconstruction techniques is critical for implementing CSBRT without compromising efficacy and safety. [ABSTRACT FROM AUTHOR]

Both spine and nonspine bone metastases are frequent sites of spread from solid organ malignancies. As bone metastases frequently cause significant morbidity for patients, it is critical to offer a treatment that can achieve rapid and durable symptomatic relief and local control, without being associated with serious risks of toxicity. Conventional palliative radiation therapy has a key treatment component in the multidisciplinary management of these patients; however, over the past decade, it has evolved to routinely deliver high biologically effective doses with precision in the form of stereotactic body radiation therapy. This change in paradigm is a result of the shifting landscape in cancer care, such that short-term pain relief is no longer the sole therapeutic aim for selected patients, and durable symptom relief and local tumor control are the goals. This review discusses the randomized prospective evidence, ongoing trials, approach to surveillance imaging, and treatment delivery for stereotactic body radiation therapy, to both spine and nonspine bone metastases, with a specific section on sacral metastases. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion The aim of this study was to clarify the safety and efficacy of breath‐hold irradiation in liver stereotactic body radiotherapy (SBRT).A retrospective analysis was conducted on 57 consecutive patients who received SBRT for hepatocellular carcinoma or liver metastases between 2013 and 2021. Breath‐hold irradiation was implemented for patients treated after April 2020.The median follow‐up period for all patients was 16.4 months (IQR: 7.36–20.9). The 2‐year overall survival rate was 64.4% (95% CI: 47.4–77.2), and the local control rate was 84.3% (95% CI: 69.7–92.3) for all patients. The 1‐year overall survival was 80.0% (95% CI: 60.8–90.5) versus 82.0% (95% CI: 53.5–93.9) in the free‐respiratory (FR) group versus the breath‐hold (BH) group, respectively (P = 0.60). The 1‐year local control rates were 78.1% (95% CI: 57.5–89.5) in the FR group and 95.7% (95% CI: 72.9–99.4) in the BH group, respectively (P = 0.16). Radiation‐induced liver injury, defined by an escalation of ≥2 in Child–Pugh score, was observed in four patients within each group (FR 13% vs. BH 15%). There were no gastrointestinal adverse events of Grade 3 or higher.Breath‐hold irradiation can be safely administered and has demonstrated clinical potential in improving local control. Further research into dose escalation using breath‐hold techniques is warranted. [ABSTRACT FROM AUTHOR]

A Prognostic Index for Liver Radiation (PILiR) for improved patient selection for stereotactic liver-directed radiotherapy (SBRT) was developed. Using a large single-center database, 195 patients treated with SBRT for local control, including 66 with hepatocellular carcinoma (HCC) and 129 with metastatic liver disease, were analyzed. Only patients ineligible for alternative treatments were included. Overall survival was 11.9 months and 9.4 months in the HCC group and metastatic groups, respectively. In the combined dataset, Child–Pugh Score (CPS) (p = 0.002), serum albumin (p = 0.039), and presence of extrahepatic disease (p = 0.012) were significant predictors of early death on multivariable analysis and were included in the PILiR (total score 0 to 5). Median survival was 23.8, 9.1, 4.5, and 2.6 months for patients with 0, 1–2, 3, and 4–5 points, respectively. In the HCC dataset, CPS (p < 0.001) and gross tumor volume (p = 0.013) were predictive of early death. In the metastatic dataset, serum albumin (p < 0.001) and primary disease site (p = 0.003) were predictive of early death. The AUC for the combined, HCC, and metastatic datasets are 0.78, 0.84, and 0.80, respectively. Poor liver function (defined by CPS and serum albumin) and extrahepatic disease were most predictive of early death, providing clinically important expected survival information for patients and caregivers. [ABSTRACT FROM AUTHOR]

Background: This multicentric, retrospective study investigated the use of stereotactic body radiotherapy (SBRT) in patients (pts) with metastatic renal cell carcinoma (mRCC) who experienced oligoprogression during a combination therapy with an immune checkpoint inhibitor (ICI) and a tyrosine–kinase inhibitor (TKI). Methods: We retrospectively evaluated 34 pts affected by oligoprogressive RCC treated with an ICI–TKI combination between January 2020 and December 2023. SBRT was delivered to each site of oligoprogressive metastatic disease. After SBRT, pts were given follow-up clinical evaluations. 6–12–18-month local control (LC) rates and median next-line treatment-free survival (NEST-FS) were the primary endpoints. The secondary endpoints were overall response rate (ORR), clinical benefits and safety. Results: After a median follow-up of 24 months, 6–12–18-month LC rates were 100%, 71% and 43%, respectively, and the median NEST-FS was 20 months. ORR was 90%, while clinical benefit was 100%. No > G2 adverse events related to SBRT were recorded. Conclusions: In our study, SBRT for oligoprogressive mRCC turned out to be a safe and useful treatment which was able to preserve current treatment. Further prospective studies are necessary to explore the effects of the ICIs–TKIs combination and SBRT upon oligoprogressive sites in mRCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic body radiotherapy (SBRT) is a treatment technique that delivers higher doses of conformal radiation precisely to specific targets. SBRT is utilized for the treatment of the more common cancers such as lung, liver and prostate malignancies, both in the early stage and the oligometastatic setting. The aim of this review is to highlight the current role of SBRT for renal cell carcinoma (RCC), a disease which was previously thought to be radioresistant, particularly to conventionally fractionated radiotherapy. There is now an increasing body of literature encompassing published phase II trials, reviews and meta-analyses demonstrating the effectiveness of SBRT in both early-stage RCC (as an alternative to patients who are not surgical candidates) and within the context of metastasis-directed therapy (MDT) for patients with oligometastatic and oligoprogressive RCC. Ongoing randomized trials are also exploring the role of SBRT as a cytoreductive treatment in metastatic RCC. Renal cell carcinoma (RCC) has been increasing in incidence by around 1.5% per year for several years. However, the mortality rate has been decreasing by 1.6% per year, and this can be attributed to stage migration and improvements in treatment. One treatment modality that has emerged in recent years is stereotactic body radiotherapy (SBRT), which is an advanced radiotherapy technique that allows the delivery of high-dose radiation to the tumor while minimizing doses to the organs at risk. SBRT has developed a role in the treatment of early-stage, oligometastatic and oligoprogressive RCC. In localized disease, phase II trials and meta-analyses have shown that SBRT provides a very high probability of long-term local control with a low risk of severe late toxicity. In oligometastatic (OMD) RCC, the same level of evidence has similarly shown good local control and minimal toxicity. SBRT could also delay the necessity to start or switch systemic treatments. Medical societies have started to incorporate SBRT in their guidelines in the treatment of localized disease and OMD. A possible future role of SBRT involves cytoreduction. It is theorized that SBRT can lower tumor burden and enhance immune-related response, but it cannot be recommended until the results of the phase II trials are published. [ABSTRACT FROM AUTHOR]

Background: The Study Group for the Biology and Treatment of the OligoMetastatic Disease on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) has conducted a national survey with the aim to depict the current patterns of practice of stereotactic body radiotherapy (SBRT) for spinal oligometastases. Methods: The Surveymonkey platform was used to send a 28-items questionnaire focused on demographic, clinical and technical aspects related to SBRT for spinal oligometastases. All the AIRO members were invited to fill the questionnaire. Data were then centralized to a single center for analysis and interpretation. Results: 53 radiation oncologists from 47 centers fulfilled the survey. A complete agreement was observed in proposing SBRT for spinal oligometastases, with the majority considering up to 3 concurrent spine oligometastases feasible for SBRT (73.5%), regardless of spine site (70%), vertebral segment (85%) and morphological features of the lesion (71.7%). Regarding dose prescription, fractionated regimens resulted as the preferred option, either in 3 (58.4%) or five sessions (34%), with a substantial agreement in applying a PTV-margin larger than 1 mm (almost 90% of participants), and ideally using both MRI and PET imaging to improve target volume and organs-at-risk delineation (67.9%). Conclusions: This national italian survey illustrates the patterns of practice and the main issues for the indication of SBRT for spinal oligometastases. A substantial agreement in the numerical cut-off and vertebral segment involved for SBRT indication was reported, with a slight heterogeneity in terms of dose prescription and fractionation schemes. [ABSTRACT FROM AUTHOR]

A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006–February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67 years old (36–92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50 Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32 Gy). The treatment response at 3–4 months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions. [ABSTRACT FROM AUTHOR]

This preliminary ethical appraisal from the STOPSTORM.eu consortium is meant to raise critical points that clinicians administering stereotactic arrhythmia radioablation should consider to meet the highest standards in medical ethics and thus promote quality of life of patients recruited for radiotherapy treatments at a stage in which they experience a significant degree of vulnerability. [ABSTRACT FROM AUTHOR]

Metastasis‐directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5‐year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT‐based MDT. The primary endpoint was 5‐year treatment escalation‐free survival (TE‐FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone‐naïve at baseline. The rate of 5‐year TE‐FS was 21.7% (95% confidence interval [CI]: 15.7%–28.7%) overall and 25.4% (95% CI: 18.1%–33.9%) in the hormone‐naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4–5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05–2.01, p =.026), a higher baseline prostate‐specific antigen (PSA) (HR = 1.06, 95% CI: 1.03–1.09, p <.001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40–3.26, p <.001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow‐up, 18.9% (95% CI: 13.2%–25.7%) of participants were free from treatment escalation (median follow‐up of 67.9 months) and two participants had an undetectable PSA level. No treatment‐related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT‐based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT‐based MDT to standard‐of‐care ADT‐based approaches are required to evaluate the impact of delaying ADT on survival. [ABSTRACT FROM AUTHOR]

Abstract Background and purpose The role of local ablative radiotherapy (stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS)) in the management of metastatic breast cancer (mBC) patients remains unclear. This study aimed to assess the efficacy of SBRT/SRS in oligometastatic and oligoprogressive breast cancer patients. Methods Totally 80 mBC patients with oligometastatic disease (OMD) and 80 with oligoprogressive disease (OPD) to ≤5 metastatic lesions were retrospectively analyzed. The endpoint was overall survival and progression-free survival, and univariate and multivariate analyses were performed for survival analysis. Results Totally 160 mBC cases (80 OMD and 80 OPD cases) were analyzed, with a total of 291 treated metastases. In the study of OMD, we analyzed 30 cases with oligo-recurrence and 50 cases with sync-oligometastases. The median follow-up time was 46 months, and 1-, 2-, and 3-year OS rates for all patients were 89.8%, 77.6%, and 67.3%, respectively, and the 1-, 2-, and 3-year PFS rates were 71.4%, 44.9%, and 34.7% respectively. In multivariate analysis (MVA), treatment for oligometastases and non-triple-negative status predicted favorable OS. In patients with oligometastases, median OS was 58 months, and 1-, 2-, and 3-year OS rates were 100%, 91.7%, and 83.3%, respectively; median OS in patients with oligoprogression was 35 months, and 1-, 2-, and 3-year OS rates were 80%, 64%, and 52%, respectively. In mBC cases with limited brain metastases administered SRS, poor OS was detected in patient age under 45 years (P = 0.041), triple-negative cases (P = 0.025), and those with OPD (P = 0.022). In OMD, a significant improvement in PFS was observed in the oligo-recurrence group compared to the sync-oligometastases group (P = 0.013). Conclusion Patients administered local ablative radiotherapy (SBRT/SRS) for oligometastases have better overall survival than those treated for oligoprogression. SBRT/SRS may be beneficial for young and non-triple-negative mBC cases. The presence of oligo-recurrence can predict a favorable prognosis of oligometastases in patients with mBC treated with SBRT/SRS.

Abstract Background The SMILE study addresses a significant need in palliative oncology by evaluating the non-inferiority of a shortened, 3-fraction stereotactic body radiotherapy (SBRT) schedule against the traditional 5-fraction approach for non-spine bone metastases in terms of pain control. Optimizing SBRT could significantly enhance the quality of life for patients by providing effective pain relief while minimizing treatment sessions. Methods This international, multicenter phase III trial will randomize 162 patients to receive either a 3-fraction regimen (9 Gy per fraction) or a standard 5-fraction regimen (7 Gy per fraction). Outcomes, assessed at 3 months post-treatment, will focus on pain response, quality of life, and control of metastasis. With a hypothesis-driven design, the study will incorporate intent-to-treat and per-protocol analyses, incorporating appropriate measures for data integrity and handling of missing information. Discussion If the 3-fraction SBRT regimen demonstrates non-inferiority, it could streamline palliative care protocols, reduce patient burden, and set a new standard for treatment, reflecting a patient-centered approach in palliative radiation oncology. Trial registration The trial has been registered prospectively on ClinicalTrials.gov under the identifier NCT05406063, as of May 3, 2022.

Abstract Background and objectives The purpose of this study was to investigate the survival benefit of Stereotactic Body Radiotherapy (SBRT) versus lenvatinib as first-line therapy in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Materials and methods 147 HCC patients with PVTT were included in this retrospective study, 70 were treated with SBRT and 77 of were treated with lenvatinib. Propensity score matching (PSM) analysis was employed to balance the differences in baseline characteristics between the two groups. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were compared between the two groups. In addition, the safety of patients in both groups was also evaluated. Results After PSM, 38 patients were matched in each of the two groups. The median OS was 14.5 (95% CI: 10.1–18.9) and 11.1 (95% CI: 9.3–12.9) months in the SBRT and lenvatinib groups, respectively (P = 0.014). The median PFS was 6.8 (95% CI: 5.1–8.5) and 5.0 (95% CI: 3.0–7.0) months, respectively (P = 0.010). The 1-, 2-years OS rates in the two groups were 65.8% vs. 39.5% and 31.6% vs. 10.5%, respectively. The 6-, 12-months PFS rates in the two groups were 57.9% vs. 44.7% and 28.9% vs. 10.5%, respectively. In addition, the SBRT group had a better ORR than the lenvatinib group (52.6% vs. 23.7%, P = 0.009). Patients with good response to SBRT had better survival. Cox proportional hazard model showed that SBRT was an important prognostic factor for OS and PFS. The incidence of hypertension (34.2% vs. 0%) was higher in the LEN group, however, both treatment modalities were well tolerated in the two groups of patients. Conclusion In HCC patients with PVTT, SBRT had a better survival benefit than Lenvatinib treatment as first-line therapy.

Background: Metastatic castration‐refractory prostate cancer (mCRPC) presents a therapeutic challenge despite advancements in treatment. Once mCRPC is attained, patients face limited survival prospects. Next‐line systemic treatment (NEST) is the standard of care for progressive mCRPC, encompassing various therapeutic options with associated toxicity and costs. In patients with oligoprogressive mCRPC, data suggest that progression‐directed therapy (PDT), such as metastasectomy or stereotactic body radiotherapy, delays the initiation of NEST. Methods and Design: The MEDCARE phase III trial aims to assess the impact of PDT on overall survival (OS) in oligoprogressive mCRPC. In this multicentric, randomised, prospective trial, we aim to randomise 246 patients in 1:1 allocation ratio between the standard‐of‐care therapy (surveillance or NEST) or PDT while continuing the current systemic treatment. Patients will be stratified based on number of progressive lesions (one vs ≥one), location of progressive lesions (local recurrence, N or M1a vs M1b or M1c) and previous systemic therapy (palliative androgen‐deprivation therapy [pADT] vs pADT + androgen receptor‐targeted agent or patients who received docetaxel in the past). The primary endpoint is OS, and the secondary endpoints include quality of life, radiographic progression‐free survival (PFS), modified PFS, prostate cancer‐specific survival and PDT‐induced toxicity. Discussion: This is the first randomised phase 3 trial in the setting of PDT in patients with oligoprogressive mCRPC with OS as the primary endpoint. [ABSTRACT FROM AUTHOR]

Background: We report on the characterization and introduction of a novel prognostic score for patients undergoing stereotactic body radiotherapy (SBRT) for the treatment of single and multiple pulmonary metastases (PMs) derived from head and neck cancer (HNC). Methods: In this retrospective study, we examined selected factors associated with progression‐free survival (PFS) and overall survival (OS) among 59 patients with HNC treated with SBRT for a total of 118 PMs, between 2009 and 2023. Factors related to survival were included in the prognostic scoring system. Results: Prognostic factors including histology, age, number of metastases, and performance status at first SBRT were weighted differently depending on the strength of correlation to PFS and OS. Total prognostic scores (HAMP) ranged from 13 to 24 points, with a cut‐off total score of ≤18 scoring points for patients in a high‐risk (HR) subcohort, and of ≥19 scoring points for patients in a low‐risk group (LR). Median PFS (23.8 vs. 5.5 months, p < 0.001) and OS (61.3 vs. 16.4 months, p < 0.001) were significantly longer in the low‐risk group compared to the high‐risk group. Conclusion: The HAMP score might be a convenient tool to facilitate individualized treatment decisions and appropriate follow‐up. The accuracy and reliability of the score requires further evaluation in prospective studies. [ABSTRACT FROM AUTHOR]

A Prognostic Index for Liver Radiation (PILiR) for improved patient selection for stereotactic liver-directed radiotherapy (SBRT) was developed. Using a large single-center database, 195 patients treated with SBRT for local control, including 66 with hepatocellular carcinoma (HCC) and 129 with metastatic liver disease, were analyzed. Only patients ineligible for alternative treatments were included. Overall survival was 11.9 months and 9.4 months in the HCC group and metastatic groups, respectively. In the combined dataset, Child–Pugh Score (CPS) (p = 0.002), serum albumin (p = 0.039), and presence of extrahepatic disease (p = 0.012) were significant predictors of early death on multivariable analysis and were included in the PILiR (total score 0 to 5). Median survival was 23.8, 9.1, 4.5, and 2.6 months for patients with 0, 1–2, 3, and 4–5 points, respectively. In the HCC dataset, CPS (p < 0.001) and gross tumor volume (p = 0.013) were predictive of early death. In the metastatic dataset, serum albumin (p < 0.001) and primary disease site (p = 0.003) were predictive of early death. The AUC for the combined, HCC, and metastatic datasets are 0.78, 0.84, and 0.80, respectively. Poor liver function (defined by CPS and serum albumin) and extrahepatic disease were most predictive of early death, providing clinically important expected survival information for patients and caregivers.

Abstract Although stereotactic body radiotherapy (SBRT) is a curative treatment option for stage I non‐small cell lung cancer (NSCLC), limited data are available regarding chest wall (CW) toxicities during an extended follow‐up of over 10 years. We report an unusual case of a bone tumor‐like CW mass lesion with pathological rib fractures observed 13 years after SBRT for peripheral lung cancer. Despite the initial suspicion of radiation‐induced sarcoma, a subsequent incisional biopsy revealed no evidence of malignancy, and a definitive diagnosis of osteonecrosis was made. Thus, long‐term observation of over 10 years is required to identify late chronic complications following SBRT.

The lung is a major dose-limiting organ for radiation therapy (RT) for cancer in the thoracic region, and the clarification of radiation-induced lung damage (RILD) is important. However, there have been few reports containing a detailed comparison of radiographic images with the pathological findings of radiation pneumonitis (RP)/radiation fibrosis (RF). We recently reported the upregulated expression of tenascin-C (TNC), an inflammation-associated extracellular matrix molecule, in surgically resected lung tissue, and elevated serum levels were elevated in a RILD patient. Therefore, we have developed a novel mouse model of partial lung irradiation and studied it with special attention paid to the computed tomography (CT) images and immunohistological findings. The right lungs of mice (BALB/c) were irradiated locally at 30 Gy/1fr, and the following two groups were created. In Group 1, sequential CT was performed to confirm the time-dependent changes in RILD. In Group 2, the CT images and histopathological findings of the lung were compared. RP findings were detected histologically at 16 weeks after irradiation; they were also observed on the CT images from 20 weeks. The immunostaining of TNC was observed before the appearance of RP on the CT images. The findings suggest that TNC could be an inflammatory marker preceding lung fibrosis.

Although stereotactic body radiotherapy (SBRT) is a curative treatment option for stage I non‐small cell lung cancer (NSCLC), limited data are available regarding chest wall (CW) toxicities during an extended follow‐up of over 10 years. We report an unusual case of a bone tumor‐like CW mass lesion with pathological rib fractures observed 13 years after SBRT for peripheral lung cancer. Despite the initial suspicion of radiation‐induced sarcoma, a subsequent incisional biopsy revealed no evidence of malignancy, and a definitive diagnosis of osteonecrosis was made. Thus, long‐term observation of over 10 years is required to identify late chronic complications following SBRT. [ABSTRACT FROM AUTHOR]

Purpose: Intraprostatic recurrence (IRR) of prostate cancer after radiation therapy is increasingly identified. Our objective was to review the literature to determine the optimal workup for identifying IRR, the management options, and practical considerations for the delivery of re-irradiation as salvage local therapy. Methods: We performed a systematic review of available publications and ongoing studies on the topics of IRR, with a focus on salvage re-irradiation. Results: Work up of biochemically recurrent prostate cancer includes PSMA PET/CT and multiparametric MRI, followed by biopsy to confirm IRR. Management options include continued surveillance, palliative hormonal therapy, and salvage local therapy. Salvage local therapy can be delivered using re-irradiation with low dose rate brachytherapy, high dose rate (HDR) brachytherapy, and stereotactic body radiotherapy (SBRT), as well as non-radiation modalities, such as cryotherapy, high-intensity focused ultrasound, irreversible electroporation and radical prostatectomy. Data demonstrate that HDR brachytherapy and SBRT have similar efficacy compared to the other salvage local therapy modalities, while having more favorable side effect profiles. Recommendations for radiation therapy planning and delivery using HDR and SBRT based on the available literature are discussed. Conclusion: Salvage re-irradiation is safe and effective and should be considered in patients with IRR. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the impact of facilitating target delineation of continuous positive airway pressure (CPAP) in patients undergoing stereotactic ablative radiation therapy (SABR) for lung tumors by lung expansion and respiratory motion management. Materials and Methods: We performed a prospective single-institutional trial of patients who were diagnosed with either primary lung cancer or lung metastases and received SABR with a dose of 40 to 60 Gy in 4 fractions. Four-dimensional computed tomography simulations were conducted for each patient: once without CPAP and again with CPAP. Results: Thirty-two patients with 39 tumors were analyzed, after the withdrawal of five patients due to discomfort. For 26 tumors separated from the diaphragm, CPAP significantly increased the superoinferior distance between the tumor and the diaphragm (5.96 cm vs. 8.06 cm; p < 0.001). For 13 tumors located adjacent to the diaphragm, CPAP decreased the overlap of planning target volume (PTV) with the diaphragm significantly (6.32 cm³ vs. 4.09 cm³; p = 0.002). PTV showed a significant reduction with CPAP (25.06 cm³ vs. 22.52 cm³, p = 0.017). In dosimetric analyses, CPAP expanded lung volume by 58.4% with a significant reduction in mean dose and V5 to V40. No more than grade 2 adverse events were reported. Conclusion: This trial demonstrated significant improvement of CPAP in target delineation uncertainties for lung SABR, with dosimetric benefits, a favorable safety profile and tolerability. Further investigation is warranted to explore the role of CPAP as a novel strategy for respiratory motion management. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) often presents with tumor thrombus (TT) in the inferior vena cava (IVC), posing significant therapeutic challenges, particularly in cases of metastatic or inoperable disease. While surgical excision remains the standard treatment approach, recent advancements in radiotherapy techniques may offer alternative strategies. We present the clinical picture of a 74-year-old male with metastatic RCC, who presented with recurrent IVC-TT, detected by surveillance computed tomography imaging, and complained of mild lower leg edema. This was successfully managed with stereotactic body radiotherapy (SBRT), resulting in a slow but continuous shrinkage of the IVC-TT with almost complete regression of most lung, liver, and lymph node metastases, obtaining a full resolution of the mild bilateral leg edema. The case described here highlights the possibility of using radiotherapy as a safe and tolerable treatment for inoperable or metastatic patients with IVC-TT. Additionally, we conducted a literature review looking for evidence of the effectiveness of radiotherapy in RCC patients with IVC-TT across different treatment settings. This case-based review ultimately aims to shed light on the emerging evidence supporting the usefulness of radiotherapy in such complex clinical challenges, hopefully paving the way for well-organized trials. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine neoplasms (NENs) are rare tumours that develop from neuroendocrine cells in various parts of the body. The management of this disease poses a significant challenge because of the heterogeneous clinical presentation and varying degrees of aggressiveness. A multidisciplinary approach is often required in complex clinical situations. Radiotherapy (RT) plays a key role in managing NETs in both curative and palliative settings. Summary: In this review, we summarize and discuss recent developments in the field of advanced RT in early-stage, locally advanced, and metastatic NENs. We highlight limitations in current approaches and discuss future potential treatment strategies for patients with NENs. [ABSTRACT FROM AUTHOR]

Background: Aging is a multifaceted process that may lead to an increased risk of developing cancer. Artificial intelligence (AI) applications in clinical cancer research may optimize cancer treatments, improve patient care, and minimize risks, prompting AI to receive high levels of attention in clinical medicine. This systematic review aims to synthesize current articles about the effectiveness of artificial intelligence in cancer treatments for older adults. Methods: We conducted a systematic review by searching CINAHL, PsycINFO, and MEDLINE via EBSCO. We also conducted forward and backward hand searching for a comprehensive search. Eligible studies included a study population of older adults (60 and older) with cancer, used AI technology to treat cancer, and were published in a peer-reviewed journal in English. This study was registered on PROSPERO (CRD42024529270). Results: This systematic review identified seven articles focusing on lung, breast, and gastrointestinal cancers. They were predominantly conducted in the USA (42.9%), with others from India, China, and Germany. The measures of overall and progression-free survival, local control, and treatment plan concordance suggested that AI interventions were equally or less effective than standard care in treating older adult cancer patients. Conclusions: Despite promising initial findings, the utility of AI technologies in cancer treatment for older adults remains in its early stages, as further developments are necessary to enhance accuracy, consistency, and reliability for broader clinical use. [ABSTRACT FROM AUTHOR]

To assess toxicity and patient quality of life after stereotactic body radiotherapy (SBRT) to oligoprogressive disease (OPD) in patients with metastatic castrate-resistant prostate cancer (CRPC) on androgen receptor targeted agents (ARTA). This phase II trial enrolled patients with metastatic CRPC with ≤ 2 oligoprogressive lesions in bone, lymph node, lung, or prostate. All patients were receiving systemic treatment with abiraterone or enzalutamide at the time of oligoprogression. All patients received SBRT to the OPD site(s) and continued the current ARTA. Patients received 30 Gy in 5 fractions (alternate days) to the OPD site. The primary endpoint of the trial is to assess if SBRT to OPD sites results in progression free survival of >6 months. The primary endpoint for this toxicity analysis is the rate of grade 3 or higher adverse events at any timepoint up to 6 months after SBRT. Secondary endpoints included comparing pre- and post-SBRT patient-related outcomes reported using visual analogue scale scores and EQ-5D health questionnaire. Forty enrolled patients had at least 6 months of follow-up at the time of analysis. Grade 3 or higher toxicity from any cause recorded using common terminology criteria for adverse events and radiation therapy oncology group was found in 8/40 (20%) of patients, but only 1/40 (2.5%) was deemed possibly related to SBRT. There was no significant difference in mean EQ5D visual analogue scale score from baseline to each timepoint after SBRT (p = 0.449). In this prospective phase II clinical trial for OPD whilst on ARTA in the CRPC setting, we report low grade ≥ 3 toxicity after SBRT. There is no discernible change in patient-reported quality of life due to SBRT treatment. The final results of progression-free survival and toxicity of SBRT treatment will be reported once further follow-up is complete. • Stereotactic radiotherapy to oligoprogressive disease in metastatic prostate cancer patients on targeted agents is feasible. • Stereotactic body radiotherapy is well tolerated in patients with castrate-resistant prostate cancer. • There is minimal treatment-related effect on quality of life and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to determine the dosimetric value of flattening filter-free (FFF) beams compared to flattening filter (FF) beams using different algorithms in the treatment planning of thoracic spine stereotactic body radiation therapy (SBRT). A total of 120 plans were created for 15 patients using the Anisotropic Analytical Algorithm (AAA) and the Acuros External Beam (AXB) algorithm with FF and FFF beams at 6 MV and 10 MV energies. Various dosimetric parameters were evaluated, including target coverage, dose spillage, and organs-at-risk sparing of the spinal cord and esophagus. Treatment delivery parameters, such as the monitor units (MUs), modulation factors (MFs), beam-on time (BOT), and dose calculation time (DCT), were also collected. Significant differences were observed in the dosimetric parameters when AXB was used for all energies (P < 0.05). 6 XFFF energy was the best option for target coverage, dose spillage, and organs-at-risk sparing. In contrast, dosimetric parameters had no significant difference when using the AAA. The AAA and AXB calculations showed that the 6 XFFF beam had the shortest DCT. The treatment delivery parameters indicated that 10 XFF beam required the fewest MUs and MFs. In addition, the 10 XFFF beam demonstrated the shortest BOT. For effective treatment of the thoracic spine using SBRT, it is recommended to use the 10 XFFF beam because of the short BOT. Moreover, the AXB algorithm should be used because of its accurate dose calculation in regions with tissue heterogeneity. [ABSTRACT FROM AUTHOR]

Background and Objectives: The recently published Spine Stereotactic Radiosurgery (SSRS) ESTRO guidelines advise against treating spinal metastatic disease with a single dose equal to or smaller than 18 Gy, prioritizing local control over the potential for complications. This study aims to assess the necessity and validity of these higher dose recommendations by evaluating the outcomes and experiences with lower radiation doses. Materials and Methods: A retrospective evaluation of SSRS patients treated at a single institute was conducted. The outcomes and complications of this cohort were compared to the current literature and the data supporting the new ESTRO guidelines. Results: A total of 149 treatment sessions involving 242 spinal levels were evaluated. The overall local control rate was 91.2%. The mean radiation dose for the local control group compared to the local failure group was similar (17.5 vs. 17.6 Gy, not significant). The overall complication rate was 6%. These results are consistent with previous publications evaluating SSRS for metastatic spinal disease. Conclusions: SSRS dose escalation may increase local control efficacy but comes with a higher risk of complications. The evidence supporting the strong recommendations in the recent ESTRO guidelines is not robust enough to justify a universal application. Given the palliative nature of treatment for metastatic patients, dose determination should be individualized based on patient conditions and preferences, with a detailed discussion about the risk–benefit ratio of increased doses and the level of evidence supporting these recommendations. [ABSTRACT FROM AUTHOR]

Purpose and objective: To develop expert consensus statements on multiparametric dose prescriptions for stereotactic body radiotherapy (SBRT) aligning with ICRU report 91. These statements serve as a foundational step towards harmonizing current SBRT practices and refining dose prescription and documentation requirements for clinical trial designs. Materials and methods: Based on the results of a literature review by the working group, a two-tier Delphi consensus process was conducted among 24 physicians and physics experts from three European countries. The degree of consensus was predefined for overarching (OA) and organ-specific (OS) statements (≥ 80%, 60–79%, < 60% for high, intermediate, and poor consensus, respectively). Post-first round statements were refined in a live discussion for the second round of the Delphi process. Results: Experts consented on a total of 14 OA and 17 OS statements regarding SBRT of primary and secondary lung, liver, pancreatic, adrenal, and kidney tumors regarding dose prescription, target coverage, and organ at risk dose limitations. Degree of consent was ≥ 80% in 79% and 41% of OA and OS statements, respectively, with higher consensus for lung compared to the upper abdomen. In round 2, the degree of consent was ≥ 80 to 100% for OA and 88% in OS statements. No consensus was reached for dose escalation to liver metastases after chemotherapy (47%) or single-fraction SBRT for kidney primaries (13%). In round 2, no statement had 60–79% consensus. Conclusion: In 29 of 31 statements a high consensus was achieved after a two-tier Delphi process and one statement (kidney) was clearly refused. The Delphi process was able to achieve a high degree of consensus for SBRT dose prescription. In summary, clear recommendations for both OA and OS could be defined. This contributes significantly to harmonization of SBRT practice and facilitates dose prescription and reporting in clinical trials investigating SBRT. [ABSTRACT FROM AUTHOR]

Background: Prior work documented circadian rhythm impacts on efficacy and toxicity of cancer therapies. Methods: Secondary analysis of prospective, phase II trial of metastatic HNSCC randomized to nivolumab+/−SBRT. Used cutoffs of 1100 and 1630. Timing classified by first infusion or majority of SBRT (e.g., PM SBRT defined by two or three fractions after 1630). Results: Of 62 patients, there was no significant difference in median PFS between AM nivolumab (n = 7, 175 days), PM nivolumab (n = 21, 58 days), or Mid‐Day nivolumab (n = 34, 67 days; p = 0.8). There was no significant difference in median PFS with AM SBRT (n = 4, 78 days), PM SBRT (n = 13, 111 days), or Mid‐Day SBRT (n = 15, 63 days; p = 0.8). There was no significant difference in Grade 3–4 toxicity or ORR. Sensitivity analyses with other timepoints were negative. Conclusions: Further work may elucidate circadian impacts on select patients, tumors, and therapies; however, we found no significant effect in this study. [ABSTRACT FROM AUTHOR]

Purpose of Review: The goal is to describe the evolution of radiation therapy (RT) utilization in the management of localized and metastatic prostate cancer. Recent Findings: Long term data for a variety of hypofractionated definitive RT dose-fractionation schemes has matured, allowing patients and providers many standard-of-care options to choose from. Post-prostatectomy, adjuvant RT has largely been replaced by an early salvage approach. Multiparametric MRI and PSMA PET have enabled increasingly targeted RT delivery to the prostate and oligometastatic tumors. Areas of active investigation include determining the value of proton beam therapy and perirectal spacers, and optimally incorporate genomic tumor profiling and next generation hormonal therapies with RT in the curative setting. Summary: The use of radiation therapy to treat prostate cancer is rapidly evolving. In the coming years, there will be continued improvements in a variety of areas to enhance the value of RT in multidisciplinary prostate cancer management. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the intra‐fractional tumor motion in lung stereotactic body radiotherapy (SBRT) with deep inspiration breath‐hold (DIBH), and to investigate the adequacy of the current planning target volume (PTV) margins. Methods: Twenty‐eight lung SBRT patients with DIBH were selected in this study. Among the lesions, twenty‐three were at right or left lower lobe, two at right middle lobe, and three at right or left upper lobe. Post‐treatment gated cone‐beam computed tomography (CBCT) was acquired to quantify the intra‐fractional tumor shift at each treatment. These obtained shifts were then used to calculate the required PTV margin, which was compared with the current applied margin of 5 mm margin in anterior‐posterior (AP) and right‐left (RL) directions and 8 mm in superior‐inferior (SI) direction. The beam delivery time was prolonged with DIBH. The actual beam delivery time with DIBH (Tbeam_DIBH) was compared with the beam delivery time without DIBH (Tbeam_wo_DIBH) for the corresponding SBRT plan. Results: A total of 113 treatments were analyzed. At six treatments (5.3%), the shifts exceeded the tolerance defined by the current PTV margin. The average shifts were 0.0 ± 1.9 mm, 0.1±1.5 mm, and ‐0.5 ± 3.7 mm in AP, RL, and SI directions, respectively. The required PTV margins were determined to be 4.5, 3.9, and 7.4 mm in AP, RL, and SI directions, respectively. The average Tbeam_wo_DIBH and Tbeam_DIBH were 2.4 ± 0.4 min and 3.6 ± 1.5 min, respectively. The average treatment slot for lung SBRT with DIBH was 25.3 ± 7.9 min. Conclusion: Intra‐fractional tumor motion is the predominant source of treatment uncertainties in CBCT‐guided lung SBRT with DIBH. The required PTV margin should be determined based on data specific to each institute, considering different techniques and populations. Our data indicate that our current applied PTV margin is adequate, and it is possible to reduce further in the RL direction. The time increase of Tbeam_DIBH, relative to the treatment slot, is not clinically significant. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review summarizes the current role of radiotherapy for the treatment of cutaneous melanoma in the definitive, adjuvant, and palliative settings, and combinations with immunotherapy and targeted therapies. Recent Findings: Definitive radiotherapy may be considered for lentigo maligna if surgery would be disfiguring. High risk, resected melanoma may be treated with adjuvant radiotherapy, but the role is poorly defined since the advent of effective systemic therapies. For patients with metastatic disease, immunotherapy and targeted therapies can be delivered safely in tandem with radiotherapy to improve outcomes. Summary: Radiotherapy and modern systemic therapies act in concert to improve outcomes, especially in the metastatic setting. Further prospective data is needed to guide the use of definitive radiotherapy for lentigo maligna and adjuvant radiotherapy for high-risk melanoma in the immunotherapy era. Current evidence does not support an abscopal response or at least identify the conditions necessary to reliably produce one with combinations of radiation and immunotherapy. [ABSTRACT FROM AUTHOR]

There are limited treatment options for recurrent advanced esophageal squamous cell carcinoma. A good response with a possible abscopal effect was observed in a patient with programmed death-ligand 1 (PD-L1)-negative recurrent advanced esophageal squamous cell carcinoma treated with an anti- PD-1 monoclonal antibody plus stereotactic body radiotherapy (SBRT). A 66-year-old male patient was diagnosed with recurrent advanced esophageal squamous cell carcinoma with multiple lung metastases (13 metastatic nodules in total) four months after completing radical radiotherapy plus concurrent and consolidated chemotherapy, and PD-L1 expression in the primary esophageal tumor was negative. This patient received 25 cycles of camrelizumab (an anti-PD-1 monoclonal antibody) in total plus upfront SBRT for two metastatic nodules, which was administered after the first cycle of camrelizumab. After this combined treatment, for most nontarget nodules, an obvious volume decrease and fuzzy change were observed, including two nodules that completely vanished. At the end of follow-up, the progression-free survival and duration of response of this patient were 34 months and 32 months, respectively. This case report indicated that an anti-PD-1 monoclonal antibody combined with SBRT was a promising therapeutic strategy for recurrent esophageal squamous cell carcinoma even in patients with negative PDL1 expression. [ABSTRACT FROM AUTHOR]

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Study Design: Retrospective Cohort Objective: Antiresorptive drugs are often given to minimize fracture risk for bone metastases, but data regarding optimal time or ability to reduce stereotactic body radiotherapy (SBRT)-induced fracture risk is limited. This study examines the association between antiresorptive use surrounding spinal SBRT and vertebral compression fracture (VCF) incidence to provide information regarding effectiveness and optimal timing of use. Methods: Patients treated with SBRT for spinal metastases at a single institution between 2009-2020 were included. Kaplan-Meier analysis was used to compare cumulative incidence of VCF for those taking antiresorptive drugs pre-SBRT, post-SBRT only, and none at all. Cox proportional hazards and Fine-Gray competing risk models were used to identify additional factors associated with VCF. Results: Of the 234 patients (410 vertebrae) analyzed, 49 (20.9%) were taking bisphosphonates alone, 42 (17.9%) were taking denosumab alone, and 25 (10.7%) were taking both. Kaplan-Meier analysis revealed a statistically significant lower VCF incidence for patients initiating antiresorptive drugs before SBRT compared to those taking none at all (4% vs 12% at 1 year post-SBRT, P =.045; and 4% vs 23% at 2 years, P =.008). On multivariate analysis, denosumab duration (HR:.87, P =.378) or dose (HR: 1.00, P =.644) as well as bisphosphonate duration (HR:.98, P =.739) or dose (HR:.99, P =.741) did not have statistical significance on VCF incidence. Conclusion: Initiating antiresorptive agents before SBRT may reduce the risk of treatment-induced VCF. Antiresorptive drugs are underutilized in patients with spine metastases and may represent a useful intervention to minimize toxicity and improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Background and purpose: Data is needed regarding the use of ultrahypofractionated radiotherapy (UHRT) in the context of prostate cancer elective nodal irradiation (ENI), and how this compares to conventionally fractionated radiotherapy (CFRT) ENI with CFRT or moderately hypofractionated radiotherapy (MHRT) to the prostate. Materials and methods: Between 2011–2019, 3 prospective clinical trials of unfavourable intermediate or high-risk prostate cancer receiving CFRT (78 Gy in 39 fractions to prostate; 46 Gy in 23 fractions to pelvis), MHRT (68 Gy in 25 fractions to prostate; 48 Gy to pelvis), or UHRT (35–40 Gy in 5 fractions to prostate +/- boost to 50 Gy to intraprostatic lesion; 25 Gy to pelvis) were conducted. Primary endpoints included biochemical failure (Phoenix definition), and acute and late toxicities (CTCAE v3.0/4.0). Results: Two-hundred-forty patients were enrolled: 90 (37.5 %) had CFRT, 90 (37.5 %) MHRT, and 60 (25 %) UHRT. Median follow-up time was 71.6 months (IQR 53.6–94.8). Cumulative incidence of biochemical failure (95 % CI) at 5-years was 11.7 % (3.5–19.8 %) for CFRT, 6.5 % (0.8–12.2 %) MHRT, and 1.8 % (0–5.2 %) UHRT, which was not significantly different between treatments (p = 0.38). Acute grade ≥ 2 genitourinary toxicity was significantly worse for UHRT versus CFRT and MHRT, but not for acute grade ≥ 3 genitourinary, or acute gastrointestinal toxicities. UHRT was not associated with worse late toxicities. Conclusion: ENI with UHRT resulted in similar oncologic outcomes to CFRT ENI with prostate CFRT/MHRT, with worse acute grade ≥ 2 GU toxicity but no differences in late toxicity. Randomized phase 3 trials of ENI using UHRT techniques are much anticipated.